ArticleProceedings of the National Academy of Sciences of the United States of America2008
Autocrine regulation of mda-7/IL-24 mediates cancer-specific apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 120 citations in OpenAlex.
- Cell Membrane Vesicles Encapsulating Il24 mRNA With Enriched CD6 Display Exhibit Enhanced Targeted Antitumor Efficacy.Journal of extracellular vesicles · 2026Article
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- IL-24 amplifies baicalein-induced immunogenic cell death in ovarian cancer by boosting endoplasmic reticulum stress.Journal of ovarian research · 2026Article
- Novel fusion superkine,Journal for immunotherapy of cancer · 2025Article
- Molecular mechanisms underlying TXNIP's anti-tumor role in breast cancer, including interaction with a novel, pro-tumor partner: CAST.Cell death & disease · 2025Article
- T helper 2 cell-directed immunotherapy eliminates precancerous skin lesions.The Journal of clinical investigation · 2025Article
- Review
- PIKFYVE inhibitors trigger interleukin-24-dependent cell death of autophagy-dependent melanoma.Molecular oncology · 2024Article
- Investigation of therapeutic potential of the Il24-p20 fusion protein against breast cancer: an in-silico approach.In silico pharmacology · 2024Article
- Interleukin 24: Signal Transduction Pathways.Cancers · 2023Review
- Article
- Integrative analysis of genomic and transcriptomic data of normal, tumour, and co-occurring leukoplakia tissue triads drawn from patients with gingivobuccal oral cancer identifies signatures of tumour initiation and progression.The Journal of pathology · 2022Article
- Enhanced Cancer Therapy Using an Engineered Designer Cytokine Alone and in Combination With an Immune Checkpoint Inhibitor.Frontiers in oncology · 2022Article
- Insights into the Mechanisms of Action of MDA-7/IL-24: A Ubiquitous Cancer-Suppressing Protein.International journal of molecular sciences · 2021Review
- Induction ofScience signaling · 2021Article
- Interleukin-24 inhibits the phenotype and tumorigenicity of cancer stem cell in osteosarcoma via downregulation Notch and Wnt/β-catenin signaling.Journal of bone oncology · 2021Article
- Engineering T Cells to Express Tumoricidal MDA-7/IL24 Enhances Cancer Immunotherapy.Cancer research · 2021Article
- Article
- Recent insights into apoptosis and toxic autophagy: The roles of MDA-7/IL-24, a multidimensional anti-cancer therapeutic.Seminars in cancer biology · 2020Review
- Mesenchymal stem cells derived from iPSCs expressing interleukin-24 inhibit the growth of melanoma in the tumor-bearing mouse model.Cancer cell international · 2020Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
A noteworthy aspect of melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) as a cancer therapeutic is its ability to selectively kill cancer cells without harming normal cells. Intracellular MDA-7/IL-24 protein, generated from an adenovirus expressing mda-7/IL-24 (Ad.mda-7), induces cancer-specific apoptosis by inducing an endoplasmic reticulum (ER) stress response. Secreted MDA-7/IL-24 protein, generated from cells infected with Ad.mda-7, induces growth inhibition and apoptosis in surrounding noninfected cancer cells but not in normal cells, thus exerting an anti-tumor "bystander" effect. The present studies reveal a provocative finding that recombinant MDA-7/IL-24 protein can robustly induce expression of endogenous mda-7/IL-24, which generates the signaling events necessary for bystander killing. To evaluate the mechanism underlying this positive autocrine feedback loop, we show that MDA-7/IL-24 protein induces stabilization of its own mRNA without activating its promoter. Furthermore, this posttranscriptional effect depends on de novo protein synthesis. As a consequence of this autocrine feedback loop MDA-7/IL-24 protein induces sustained ER stress as evidenced by expression of ER stress markers (BiP/GRP78, GRP94, GADD153, and phospho-eIF2alpha) and reactive oxygen species production, indicating that both intracellular and secreted proteins activate similar signaling pathways to induce apoptosis. Thus, our results clarify the molecular mechanism by which secreted MDA-7/IL-24 protein (generated from Ad.mda-7-infected cells) exerts cancer-specific killing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.